U.S. patent number 5,565,207 [Application Number 08/311,448] was granted by the patent office on 1996-10-15 for scalp moisturizer and external skin preparation.
This patent grant is currently assigned to Pola Kasei Kogyo Kabushiki Kaisha. Invention is credited to Nobuo Kashibuchi, Yoshio Kitada, Kenkichi Matsubara, Hiroyuki Suzuki.
United States Patent |
5,565,207 |
Kashibuchi , et al. |
October 15, 1996 |
Scalp moisturizer and external skin preparation
Abstract
A scalp-moisturizer or external skin preparation containing as
essential active ingredients the following: (a) steroid glycoside
and/or triterpenoid glycoside, (b) sphingo glycolipid and (c)
steroid hormone, the content of (a) and (b) being 0.01-10% by
weight of the total, the (a)/(b) ratio by weight being 85/15-30/70
and (c) being incorporated in effective amounts of not more than
0.1% by weight of the total.
Inventors: |
Kashibuchi; Nobuo
(Kanagawa-ken, JP), Matsubara; Kenkichi
(Kanagawa-ken, JP), Kitada; Yoshio (Kanagawa-ken,
JP), Suzuki; Hiroyuki (Kanagawa-ken, JP) |
Assignee: |
Pola Kasei Kogyo Kabushiki
Kaisha (Shizuoka-ken, JP)
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Family
ID: |
27478059 |
Appl.
No.: |
08/311,448 |
Filed: |
September 26, 1994 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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990238 |
Dec 14, 1992 |
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755134 |
Sep 5, 1991 |
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Foreign Application Priority Data
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Sep 19, 1990 [JP] |
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2-247157 |
Jul 18, 1991 [JP] |
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3-268135 |
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Current U.S.
Class: |
424/401; 424/74;
514/852; 514/880; 514/881 |
Current CPC
Class: |
A61K
8/68 (20130101); A61Q 5/00 (20130101); A61Q
19/00 (20130101); A61K 8/63 (20130101); A61Q
5/006 (20130101); Y10S 514/852 (20130101); Y10S
514/881 (20130101); Y10S 514/88 (20130101) |
Current International
Class: |
A61K
8/68 (20060101); A61K 8/30 (20060101); A61K
007/00 () |
Field of
Search: |
;424/401,47,74,195.1
;514/880,881,874,852,179,844 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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61-289013 |
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Dec 1986 |
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JP |
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62-072604 |
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Apr 1987 |
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JP |
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62-187404 |
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Aug 1987 |
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JP |
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63-192703 |
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Aug 1988 |
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JP |
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1-040412 |
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Feb 1989 |
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JP |
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2-006403 |
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Jan 1990 |
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JP |
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Other References
The Merck Manual, 15th Ed. Berkow et al, pp. 2247-2253, 2258, 2259
(1987). .
Keshohin-Kagaku Guidebook (The Society of Cosmetic Chemists of
Japan, pp. 152-153. .
Holzle et al (1977) The Journal of Investigative Dermatology
68:350-56. .
Nikko Handbook, pp. 298-313. .
Grove et al (1983) in Marks et al eds., Stratum Corneum,
Springer-Verlag, NY pp. 191-195..
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Primary Examiner: Bleutoe; John C.
Assistant Examiner: Harrison; Robert H.
Attorney, Agent or Firm: Birch, Stewart, Kolasch &
Birch, LLP
Parent Case Text
This application is a continuation of application Ser. No.
07/990,238 filed on Dec. 14, 1992, now abandoned, which is a
continuation-in-part of application Ser. No. 07/755,134, filed on
Sep. 5, 1991, now abandoned.
Claims
What is claimed is:
1. A scalp moisturizer preparation, comprising (a) a steroid
glycoside and/or a triterpenoid glycoside, (b) a sphingo glycolipid
and (c) a follicular hormone and/or an adrenocortical hormone, the
content of (a) and (b) being 0.01-10% by weight of the total, the
(a)/(b) ratio by weight being 85/15-30/70 and (c) being
incorporated in effective amounts of not more than 0.1% by weight
of the total, wherein said scalp moisturizer preparation which is
effective in suppressing dandruff and providing the hair with
moisture through the normalization and retardation of the turnover
of the scalp stratum corneum.
2. The scalp moisturizer as claimed in claim 1, further comprising
one or more sebum secretion inhibitors and/or antibacterial agents
with potent antibacterial activity against the microbe Pityrosporum
ovale.
3. An external skin preparation, comprising (a) a steroid glycoside
and/or a triterpenoid glycoside, (b) a sphingo glycolipid and (c) a
follicular hormone and/or an adrenocortical hormone, the content of
(a) and (b) being 0.01-10% by weight of the total, the (a)/(b)
ratio by weight being 85/15-30/70 and (c) being incorporated in
effective amounts of not more than 0.1% by weight of the total,
wherein said external skin preparation is effective in promoting
the recovery of the regularity of the cellular arrangement of
corneocytes through the normalization and retardation of the
turnover of the stratum corneum.
4. The external skin preparation as claimed in claim 3, further
comprising at least one member selected from the group consisting
of an anti-inflammatory agent, a cell activator, a peroxidized
lipid formation inhibitor, and a humectant, the cell activator
being selected from the group consisting of allantoin, and an
extract of Japanese Angelica, rosemary and placentas.
5. The external skin preparation as claimed in claims 3 or 4,
wherein at least one member selected from the group consisting of
allantoin, and an extract of Japanese Angelica, rosemary or
placentas is additionally incorporated in an effective amount for
activation of dermal cells.
6. The scalp moisturizer as claimed in claim 1, wherein the content
of (a) and (b) is in the range from 0.5 to 2.0% by weight of the
total.
7. The external skin preparation as claimed in claim 3, wherein the
content of (a) and (b) is in the range from 0.5 to 2.0% by weight
of the total.
8. The preparation of claims 1 or 3, wherein said steroid glycoside
is a member selected from the group consisting of campesterol
glycoside, stigmasterol glycoside, B-sitosterol glycoside,
cholesterol glycoside, stigmasterol glycoside and avenasterol
glycoside.
9. The preparation of claims 1 or 3, wherein said triterpenoid
glycoside is a member selected from the group consisting of
cycloartenol glycoside, 24 -methylenecycloartenol glycoside,
cycloartanol glycoside, cyclobranol glycoside, glycyrrhizin and
ginsenoside.
10. The preparation of claims 1 or 3, wherein said sphingo
glycolipid contains a dihydrosphingosine, sphingosine,
phytosphingosine, or dehydrophytosphingosine skeleton.
11. The preparation of claims 1 or 3, wherein said sphingo
glycolipid is a member selected from the group consisting of a
monohexosylceramide, a sphingoplasmalogen, a monohexosylceramide
fatty acid ester, a dihexosylceramide, a trihexosylceramide, a
galactosyl-ceramide sulfate, a dihexosyl-ceramide sulfate, a
globoside, N-acetylgalactosamine-(1.fwdarw.4) D-galactosyl
(1.fwdarw.4) D-glucosyl (1.fwdarw.) ceramide, D-galactosyl
(1.fwdarw.3) N-acetylgalactosamine (1.fwdarw.4) D-galactosyl
(1.fwdarw.4) glucosyl (1.fwdarw.) ceramide, D-galactosyl
(1.fwdarw.3) D-galactosyl (1.fwdarw.3) N-acetylglucosamine
(1.fwdarw.3) D-galactosyl (1.fwdarw.4) D-glucosyl (1.fwdarw.)
ceramide, a hematoside, and a ganglioside containing both sialic
acid and hexosamine in addition to neutral glucide.
12. The preparation of claims 1 or 3, wherein the (a)/(b) ratio by
weight is 60/40-85/15.
13. The preparation of claims 1 or 3, wherein component (c) is
present in an amount in the range from 0,001-0.1% by weight of the
total composition.
14. The preparation of claim 11, wherein said monohexosylceramide
fatty acid ester is a member selected from the group consisting of
galactosylceramide fatty acid ester and glycosylceramide fatty acid
ester; said dihexosylceramide is a member selected from the group
consisting of D-galactosyl(1.fwdarw.4)D-glycosyl (1.fwdarw.)
ceramide and D-galactosyl (1.fwdarw.4) D-galactosyl (1.fwdarw.)
ceramide; said trihexosylceramide is D-galactosyl (1.fwdarw.4)
D-galactosyl (1.fwdarw.4)D-glucosyl (1.fwdarw.) ceramide; said
globoside is N-acetylgalactosamine (1.fwdarw.3) D-galactosyl
(1.fwdarw.4) galactosyl (1.fwdarw.4) D-glucosyl (1.fwdarw.)
ceramide; and said hematoside is a member selected from the group
consisting of N-acetylneuraminic acid (2.fwdarw.3) D-galactosyl
(1.fwdarw.4) D-glucosyl (1.fwdarw.)ceramide and N-acetylneuraminic
acid (2.fwdarw.3) D-galactosyl (1.fwdarw.)ceramide.
Description
FIELD OF THE INVENTION
This invention relates first of all to a scalp moisturizer. More
particularly it is directed to a scalp moisturizer of new
formulation having incorporated therein those glycosides,
glycolipids etc. which are excellent in the effects of suppressing
dandruff production in the scalp and providing the hair with
moisture.
The present invention further relates to an external skin
preparation. More particularly it provides an external skin
preparation having such an action as to normalize the skin
physiology and thereby recover the regularity of cellular
arrangement of corneocytes through the normalization and
retardation of the turnover of the stratum corneum, and thus
showing an action of improving skin-roughening.
Scalp moisturizers are believed to have different effects such as
impartation of aroma and refreshing feel to the scalp or hair and
action on the hair root, or on the skin as such, to accelerate the
hair growth or to suppress dandruff production or itching. The
major cause for the production of dandruff and itching is
considered to be the abnormal desquamation and sebum secretion
acceleration, and growth of microorganisms is pointed out to be an
aggravating factor (see, for example, Keshohin-Kagaku Guidebook,
edited by Nippon Keshohin Gijutsusha Kai, Yakuji Nipposha Co., Ltd.
p. 152).
Heretofore, shampoos having incorporated therein different
sulfur-containing compounds with antibacterial activity have
frequently been used for removal of dandruff. Also commercially
available for the same purpose are tonic agents wherein in addition
to antibacterials various vitamins or anti-histaminics such as
diphenylhydrazine hydrochloride are incorporated in different
appropriate combinations as scalp moisturizers/hair growth
accelerator (see, for example, Hifu To Biyo, 9[2] p. 1371 (1977)).
For the purpose of providing the hair with moisture, on the other
hand, hair rinses are in use which contain cationic surfactants or
humectants as active ingredients.
The performance of such products now put on the market have both
advantages and disadvantages, and they are unsatisfactory for use
as scalp moisturizers. Further, little has been known as to scalp
moisturizers, based on their action on the scalp to normalize its
physiology.
Furthermore, according to the present invention, there is provided
a novel external skin preparation. Prior art external skin
preparations which claim to be effective in improving
skin-roughening base their effect, in the majority of cases, on the
action of retaining moisture in the skin. The retaining of the skin
moisture can be effected either by suppressing transepidermal water
loss (T.W.L.) with blocking agents or by enhancing the skin
hydration effect with humectants.
The former method utilizes vaseline-based ointments or water-in-oil
type emulsions as substances or materials of high coherence with
the skin and hydrophobicity. Such substances or materials, however,
are associated with drawbacks of giving an unpleasant, e.g. oily or
greasy, sense of touch.
The latter method employs emulsified compositions containing
humectants of excellent hygroscopic and humectic capacity as
typified by polyhydric alcohols such as sorbitol, maltitol,
ethylene glycol, propylene glycol, 1,3-butylene glycol or glycerin,
urea or salts of organic acids such as sodium
pyrrolidonecarboxylate or sodium lactate. This method has the
drawback that if the effect is to be enhanced large amounts of
these substances have to be incorporated with the result that an
unpleasant, e.g., greasy or slimy, sense of touch is produced.
Furthermore, neither method is able to recover the regularity of
cellular arrangement of corneocytes.
In Japanese Laid open Patent Appln. Sho. 62-187404 (Unexamined
Patent Application Publication No. 187404/87) is described that
cosmetics having incorporated therein specific amounts of sphingo
glycolipid and steroid glycoside and/or triterpenoid glycoside are
excellent in the function of retaining moisture. With these
cosmetics, the turnover of the stratum corneum can be normalized
but the recovery of the regularity of cellular arrangement of
corneocytes cannot be expected.
In E. Holzle & G. Plewig, J. Invest. Dermatol., 68, 350 (1977)
is disclosed that when adrenocortical hormones were topically
applied to the skin and observed for changes in the morphology of
corneocytes they were found in particular to contribute to the
retardation of their turnover. No clear reference, however, is made
as to the recovery of the regularity of the cellular arrangement of
corneocytes.
Nikko Handbook (published by Nikko Chemicals Co., Ltd.) describes
that estrogen (follicular hormone) inhibits dermal growth. Nothing,
however, is described therein as to recovery of the regularity of
the cellular arrangement of corneocytes.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a scalp
moisturizer which exhibits the effects of suppressing dandruff
formation in the scalp and providing the hair with moisture,
through the normalization and retardation, as a result of the scalp
physiology being normalized, of the turnover of scalp stratum
corneum, to recover the regularity of the cellular arrangement of
corneocytes and improve multi-layer desquamation.
As a result of their extensive research to explore a scalp
moisturizer having a high dandruff-suppressive effect, the present
inventors have found those substances which are effective in
recovering the regularity of the cellular arrangement of scalp
corneocytes and improving multi-layer desquamation.
Thus, according to the present invention, there is provided a scalp
moisturizer which comprises (a) steroid glycoside and/or
triterpenoid glycoside, (b) sphingo glycolipid and (c) steroid
hormone, the content of (a) and (b) being 0.01-10% by weight of the
total, the (a)/(b) ratio by weight being 85/15-30/70 and (c) being
incorporated in effective amounts of not more than 0.1% by weight
of the total. There is further provided, as a preferred embodiment,
a scalp moisturizer which contains, in addition to the ingredients
mentioned above, one or more of sebum secretion inhibitors and/or
potent antibacterials against the microbe Pityrosporum ovale.
Another object of the present invention is to provide an external
skin preparation which exhibits the effect of improving
skin-roughening, as a result of the scalp physiology being
normalized through the normalization and retardation of the of the
stratum corneum, to recover the regularity of the cellular
arrangement of corneocytes and to improve multi-layer
desquamation.
As a result of their extensive research on the recovery of the
regularity of cellular arrangement of skin corneocytes, the present
inventors have succeeded in developing an external skin preparation
which exhibits a remarkable effect of improving skin-roughening.
Thus, according to the present invention, there is provided an
external skin preparation which comprises (a) steroid glycoside
and/or triterpenoid glycoside, (b) sphingo glycolipid and (c)
steroid hormone, the content of (a) and (b) being 0.01-10% by
weight of the total, the (a) /(b) ratio by weight being 85/15-30/70
and (c) being incorporated in effective amounts of not more than
0.1% by weight of the total. There is further provided, as a
preferred embodiment, an external skin preparation which contains,
in addition to the ingredients mentioned above, one or more of an
anti-inflammatory agent, cell activator, peroxidized lipid
formation inhibitor and humectant.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1-4 are graphs showing the results of comparative
measurements of the normalization and retardation of stratum
corneum turnover with an example of the external skin preparation
of the present invention and comparative examples of external skin
preparations.
DETAILED DESCRIPTION OF THE INVENTION
The present invention will now be described in detail in the
following.
Examples of the steroid glycoside mentioned above for use in the
scalp moisturizer or external skin preparation of the present
invention include campesterol glycoside, stigmasterol glycoside,
.beta.-sitosterol glycoside, cholesterol glycoside, stigmastenol
glycoside and avenasterol glycoside.
Examples of the triterpenoid glycoside mentioned above for use in
the scalp moisturizer or the external skin preparation of the
present invention include cycloartenol glycoside,
24-methylenecycloartenol glycoside, cycloartanol glycoside,
cyclobranol glycoside, glycyrrhizin and ginsenoside.
The sphingo glycolipids mentioned above for use in the scalp
moisturizer or external skin preparation of the present invention
are a class of glycolipids, i.e. substances containing both fatty
acid and glucide in the molecule, which have therein the
sphingosine skeleton as represented by dihydrosphingosine,
sphingosine, phytosphingosine, dehydrophytosphingosine etc.
Examples of the sphingo glycolipid include monohexosylceramide
(cerebroside), sphingoplasmalogen, monohexosylceramide fatty acid
ester (cerebroside ester) such as galactosylceramide fatty acid
ester or glycosylceramide fatty acid ester, dihexosylceramide Such
as D-galactosyl (1.fwdarw.4)D-glycosyl (1.fwdarw.) ceramide or
D-galactosyl (1.fwdarw.4)D-galactosyl (1.fwdarw.) ceramide,
trihexosylceramide such as D-galactosyl (1.fwdarw.4)D-galactosyl
(1.fwdarw.4)D-glucosyl (1.fwdarw.) ceramide, galactosyl-ceramide
sulfate (cerebroside sulfate, i.e. sulfatide), dihexosyl-ceramide
sulfate, globoside such as N-acetylgalactosamine
(1.fwdarw.3)D-galactosyl (1.fwdarw.4)D-galactosyl
(1.fwdarw.4)D-glucosyl (1.fwdarw.)ceramide [globoside I],
N-acetylgalactosamine-(1.fwdarw.4)D-galactosyl
(1.fwdarw.4)D-glucosyl (1.fwdarw.) ceramide, D-galactosyl
(1.fwdarw.3)N-acetylgalactosamine (1.fwdarw.4)D-galactosyl
(1.fwdarw.4)glycosyl (1.fwdarw.) ceramide or D-galactosyl
(1.fwdarw.3)D-galactosyl (1.fwdarw.3)N-acetylglucosamine
(1.fwdarw.3)D-galactosyl (1.fwdarw.4)D-glucosyl
(1.fwdarw.)ceramide, hematoside such as N-acetylneuraminic acid
(2.fwdarw.3)D-galactiosyl (1.fwdarw.4)D-glucosyl
(1.fwdarw.)ceramide or N-acetylneuraminic acid
(2.fwdarw.3)D-galactosyl (1.fwdarw.) ceramide, and ganglioside
containing both sialic acid and hexosamine in addition to neutral
glucide.
In incorporating steroid glycoside and/or triterpenoid glycoside
and sphingo glycolipid into the scalp moisturizer or external skin
preparation of the present invention, each of the components may be
incorporated as appropriate upon preparation of the scalp
moisturizer or external skin preparation. In order to enhance the
effects of the scalp moisturizer or external skin preparation, it
is preferable first to heat steroid glycoside and/or triterpenoid
glycoside and sphingo glycolipid in the presence of an appropriate
organic solvent and then to distill off the solvent from the
resultant solution to afford an integrated product which is then
added to an oil phase prior to use.
Steroid glycoside, triterpenoid glycoside and sphingo glycolipid
are all contained in natural materials widely occuring in the
animal and plant kingdoms. Therefore, from the industrial
perspective, it is most preferable to use extracts as such obtained
from these natural materials using organic solvents. In such cases,
however, the content of steroid glycoside, triterpenoid glycoside
and sphingo glycolipid will be dependent upon the species, part
etc. of the plant or animal used as raw materials. It follows that
the choice of raw materials is important since the ratio in the
resultant extract of (steroid glycoside+triterpenoid
glycoside)/sphingo glycolipid is an important element of the
present invention.
Examples of materials which meet the conditions in respect of the
ratio mentioned above include rice bran, wheat bran (wheat embryo
bud), millet, barnyard grass, soybean, kaoliang and corn, and these
materials can be preferably used as raw materials for the scalp
moisturizer or external skin preparation of the present
invention.
In extracting mixtures of steroid glycoside and/or triterpenoid
glycoside and sphingo glycolipid from these plant materials, any
appropriate procedure may be employed. For example, the raw
materials may be subjected, after being pretreated if necessary, to
extraction with organic solvents such as chloroform, methanol,
butanol or isopropanol, used alone or as mixtures, followed by
separation and recovery, for example by way of column
chromatography.
In the scalp moisturizer or external skin preparation, there are
incorporated one or more ingredients selected from steroid
glycosides and triterpenoid glycosides, and one or more ingredients
selected from a class of sphingo glycolipids, in amounts of
0.01-10% preferably 0.5-2.0% by weight based on the total weight of
the composition.
The (a) steroid glycoside and/or triterpenoid glycoside/(b) sphingo
glycolipid ratio by weight is 85/15-30/70. With larger amounts of
(a) beyond this range, its solubility in bases for the scalp
moisturizer or external skin preparation becomes lower. As a result
of this no satisfactory effect of dandruff suppression can be
achieved with the so obtained scalp moisturizer and also no
satisfactory effect of improving skin-roughening with the so
obtained external skin preparation. With lesser amounts of (a)
below the range, no satisfactory effect of dandruff suppression can
be achieved with the so obtained scalp moisturizer and also no
satisfactory effect of improving skin-roughening with the so
obtained external skin preparation. As the most preferable range
there may be mentioned 60/40-85/15.
In the following will now be shown some examples of preparation
where mixtures of the steroid glycoside, triterpenoid glycoside and
sphingo glycolipid mentioned above are obtained from plant
materials by extraction with organic solvents.
Preparation 1
As a pretreatment, wheat bran was extracted with hexane and the
resultant oil was treated with sulfuric acid to obtain a
precipitate. The thus formed precipitate (100 g) was treated with a
mixed solvent (1 l) of chloroform/methanol (=1/1) and the solids
were filtered off. The filtrate was concentrated under reduced
pressure and methanol (200 ml) was added to the resultant
concentrate for redissolution. Insolubles were filtered off and the
filtrate was applied on a silica gel column chromatography. As
eluting solvents, chloroform/methanol (=95/5) was first used to
elute neutral lipid, cholesterol, fatty acid etc. and
chloroform/methanol (=75/25) then used to elute a mixture of
sphingo glycolipid, steroid glycoside and triterpenoid glycoside.
Yield 0.7 g. Component ratio of mixture:
(Steroid glycoside+triterpenoid glycoside)/sphingo
glycolipid=80/20
Preparation 2
As a pretreatment, rice bran was extracted with hexane, and the
resultant oil was treated with sulfuric acid to obtain a
precipitate. The thus formed precipitate (100 g) was treated with a
mixed solvent (1 l) of chloroform/methanol (=2/1) and the solids
were filtered off. The filtrate was concentrated under reduced
pressure and chloroform (100 ml) was added to the resultant
concentrate for redissolution. The solution was a applied on a
silica gel column chromatography. As eluting solvents,
chloroform/methanol (=9/1) was first use, J to elute neutral lipid,
cholesterol, fatty acid etc. and chloroform/methanol (=8/2) then
used to elute a mixture of the desired sphingo glycolipid, steroid
glycoside and triterpenoid glycoside. Yield 1 g. Results of T.L.C.
analysis (developing solvent: benzene/ethanol=5/1)
______________________________________ Rf values 0.25-0.28 (sphingo
glycolipid) 0.32-0.35 (steroid glycoside + triterpenoid glycoside)
Component ratio of mixture: (Steroid glycoside + triterpenoid
glycoside)/ Sphingo glycolipid = 70/30)
______________________________________
As steroid hormones suitable for use in the scalp moisturizer or
external skin preparation may be mentioned follicular hormones and
adrenocortical hormones. Examples of follicular hormones include
estradiol and its esters, estrone and ethynylestradiol, and those
of adrenocortical hormones include cortisone and its esters,
hydrocortisone and its esters, prednisone and predenisolone. Any
commercially available products of these steroid hormones may be
used as such or after further processing.
In the scalp moisturizer or external skin preparation of the
present invention are incorporated one or more of the steroid
hormones mentioned above in effective amounts not more than 0 1%
preferably in the range of 0.001-0.1% by weight of the total.
The scalp moisturizer according to the present invention may
contain additional active ingredients other than the essential
active ingredients mentioned above. A preferred example of such
ingredient is sebum secretion inhibitor. Examples of sebum
secretion inhibitor include pantetheine, vitamin B.sub.6,
anti-androgenics and organic solvent extracts of ginseng, Citrus
Unshiu or Houthuyniae Herba.
Likewise as potent antibacterials against the microbe Pityrosporum
ovale to be incorporated into preferred embodiments of the scalp
moisturizer of the present invention may be used any known such
materials as such or in further processed forms. Examples of such
antibacterials include sulfur, sulfur compounds such as cadmium
sulfide or zinc pyridinium-1-thiol-N-oxide (Zpt), triclosan,
halocarban, menthols, undecylenic acid, resorcin,
isopropylmethylphenol and salicylic acid.
Other ingredients which may be incorporated into the scalp
moisturizer in accordance with the present invention include those
which are customarily used in scalp moisturizers, for example
hydrocarbons, waxes, fats and oils, esters, higher fatty acids,
higher alcohols, surfactants, perfumes, coloring matters,
antioxidants, sunscreening agents, alcohols and buffer solutions
for pH adjustment.
Furthermore, other active ingredients of different types may be
incorporated into the scalp moisturizer of the present invention in
accordance with its particular use, for example, anti-inflammatory
agents such as glycyrrhizic acid or bisabolol,
1-methyl-4-(1-hydroxyl-1,5,5-trimethyl-4-pentenyl)cyclohex-1-ene,
cell activators such as allantoin or placental extracts,
peroxidized lipid formation inhibitors such as vitamin E or
superoxide dismutase (SOD), humectants such as sodium hyaluronate
or blood circulation accelerators such as vitamin E nicotinate.
The external skin preparation according to the present invention
may contain additional active ingredients other than the essential
active ingredients mentioned above. Examples of anti-inflammatory
agents which is one of such additional ingredients include
glycyrrhezic acid or its derivatives, glycyrrhizic acid or its
derivatives, bisabolol,
1-methyl-4-(1-hydroxyl-1,5,5-trimethyl-4-pentenyl)cyclohex-1-ene
and extracts from geranii herba, horse chestnut, Japanese Angelica
or aloe.
Likewise, as examples of cell activators which are to be
incorporated into preferred embodiments of the external skin
preparation of the present invention may be mentioned allantoin or
its derivatives, or extracts from biological materials such as
Japanese Angelica, rosemary or placentas.
Likewise, as examples of peroxidized lipid formation inhibitor
which may be incorporated may be mentioned vitamin E, superoxide
dismutase (SOD) and tannins.
Likewise, as examples of humectant which may be incorporated may be
mentioned sodium hyaluronate and collagen.
Other ingredients which may be incorporated into the external skin
preparation of the present invention are those which are
customarily used in topical skin agents, for example hydrocarbons,
waxes, fats and oils, esters, higher fatty acids, preservatives,
antioxidants, sunscreening agents, alcohols and higher alcohols,
surfactants, perfumes, coloring matters, buffer solutions for pH
adjustment. Further active ingredients of different types may also
be incorporated in accordance with the particular use of the
external skin preparation of the present invention.
The scalp moisturizer of the present invention may take different
forms, for example, scalp essences, shampoos or tonics.
The external skin preparation of the present invention may also
take different forms, for example, creams, emollient lotions,
moisturizing lotions, gels or ointments.
In the following will now be described the present invention in
more detail with reference to examples of the present invention as
well as comparative examples for the purpose of comparison. It is
to be understood that the present invention be by no means limited
by these examples. The numerical values for amounts incorporated
are in parts by weight.
[Scalp Moisturizer]
Examples 1-7 and 15 and Comparative Examples 1-2 and 6 relate to
scalp moisturizer.
Examples 1-4 and Comparative Example 1
Scalp essence is prepared.
Formulation is shown in Table 1.
TABLE 1 ______________________________________ Formulation of Scalp
Essence Compa- rative Example Example Raw materials 1 2 3 4 1
______________________________________ (1) Squalane 3.0 3.0 3.0 3.0
3.0 Methylpolysiloxane 0.3 0.3 0.3 0.3 0.3 Propyl para- 0.05 0.05
0.05 0.05 0.05 hydroxybenzoate Polyoxyetylene 1.5 1.5 1.5 1.5 1.5
behenyl ether (20 E.O.) Sorbitan monostearate 0.7 0.7 0.7 0.7 0.7
Product from 2.0 2.0 2.0 2.0 -- Preparation 2 (2) Xantane gum 0.3
0.3 0.3 0.3 0.3 Methyl para- 0.3 0.3 0.3 0.3 0.3 hydroxybenzoate
Glycerin 15.0 15.0 15.0 15.0 15.0 Purified water 76.749 76.74 76.72
76.62 78.75 (3) Estrone 0.001 0.01 0.01 0.01 -- Resorcin -- -- 0.02
0.02 Pantethine -- -- -- 0.1 -- Perfume 0.1 0.1 0.1 0.1 0.1
______________________________________
Method of Preparation
By heating at 80.degree. C. raw materials indicated in (1) in Table
1 and those indicated in (2), respectively, to obtain the solution
from (1) and the solution (2). A part of the solution from (2), is
slowly added with stirring to the solution from (1) and after
reversal emulsification the remainder of the solution from (2) is
added. The mixture is cooled down to 40.degree. C. with stirring
and after addition of the raw materials indicated in (3) in Table 1
further down to 30.degree. C.
Example 15 and Comparative Example 6
Scalp essence is prepared.
Formulation is shown in Table 12.
TABLE 12 ______________________________________ Formulation of
Scalp Essence Comparative Example Example Raw materials 15 6
______________________________________ (1) Squalane 3.0 3.0
Methylpolysiloxane 0.3 0.3 Propyl para- 0.05 0.05 hydroxybenzoate
Polyoxyethylene behenyl 1.5 1.5 ether (20 E.O.) Sorbitan
monostearate 0.7 0.7 Steroid glycoside and 1.0 0 triterpenoid
glycoside Sphingo glycolipid 1.0 0 (2) Xantane gum 0.3 0.3 Methyl
para- 0.3 0.3 hydroxybenzoate Glycerin 15.0 15.0 Purified water
76.73 78.73 (3) Hydrocortisone 0.02 0.02 Perfume 0.1 0.1
______________________________________
Method of Preparation
The raw materials indicated in (1) in Table 12 and those indicated
in (2) in Table 12 shown above are separately dissolved by heating
them at 80.degree. C. A part of the solution from (2) is slowly
added with stirring to the solution from (1) and after reversal
emulsification the remainder of the solution from (2) is added. The
mixture is cooled down to 40.degree. C. and after addition of the
raw materials in (3) further down to 30.degree. C.
Results of the following tests A, B and C are shown which were
carried out with the scalp essences formulated in accordance with
Examples 1-4 and 15 and Comparative Examples 1 and 6 shown above
and those of test A are also shown which was carried with the scalp
essences formulated in accordance with Example 15 and Comparative
Example 6:
A: Test for the recovery of regularity of cellular arrangement of
scalp corneocytes and for the improvement in multi-layer
desquamation
B: Visual observation of scalp lesions
C: Test for hair moisturizing effect
A. Test for the recovery of regularity of cellular arrangement of
scalp corneocytes and for the improvement in multi-layer
desquamation
Samples
Scalp essences from Examples 1-4 and 15 and Comparative Examples 1
and 6
Procedure
(1) Healthy male subjects to be tested in their twenties to forties
have their hair cut with a hair-cutter and then get their head
shaved with a shaver. There are used fifteen for Examples 1-4 and
Comparative Example 1 and ten such subjects for Example 15 and
Comparative Example 6. A 24-hours closed patch test is carried out
by sticking on seven different sites of the scalp filter paper
disks of 1.9 cm in diameter each containing 0.1 ml of an aqueous
solution of 0.5% (w/v) sodium lauryl sulfate.
By this treatment are produced lesions in the scalp as well as
disturbances in the regularity of cellular arrangement of scalp
surface corneocytes.
(2) After the treatment (1), the closed patches are removed.
Samples are applied twice a day, i.e. in the morning (at nine
o'clock) and in the evening (at seventeen o'clock), from the
following day for two consecutive months for Examples 1-4 and
Comparative Example 6 and for one month for Example 15
and[Comparative Example 6. The hair is removed if necessary. In
order to take into account and avoid site to site variations, the
site of application is changed by rotation for each subject. The
rate of daily recovery is determined by observing specimens of the
stratum corneum, obtained from the scalp surface with an adhesive
tape, for cellular arrangement of corneocytes and multi-layer
desquamation.
Method of Evaluation
(1) The regularity of cellular arrangement of scalp corneocytes is
judged by the following five-grade rating:
Score
1. The cell shape is extremely uniform, and the cellular
arrangement is extremely regular.
2. The cell shape is uniform, and the cellular arrangement is
regular.
3. The cell shape is slightly ununiform, and the cellular
arrangement is intermediate.
4. The cell shape is ununiform, and the cellular arrangement is
irregular.
5. The cell shape is entirely ununiform, and the cellular
arrangement is extremely irregular.
The smaller the numerical rating score, the higher the rate of
recovery is in terms of the regularity of cellular arrangement of
corneocytes.
(2) The multi-layer desquamation is judged by the following
five-grade rating.
Score
1. Small number (less than 5% of all) of cells are multi-layered
and densely stained.
2. Small number (5-10% of all) of cells are multi-layered and
densely stained.
3. Slightly large number (10-25% of all) of cells are multi-layered
and densely stained, and small number of cells are peeling in
masses.
4. Large number (25-50% of all) of cells are multi-layered and some
of them are peeling in masses.
5. Large number (50% or more of all) of cells are multi-layered and
masses of peeling cells are scattered all over.
The smaller the numerical score is, the less the multi-layer
desquamation of the stratum corneum is.
A. Test for the recovery of regularity of cellular arrangement of
scalp corneocytes and for the improvement in multi-layer
desquamation
Results
TABLE 2 ______________________________________ Results of tests for
the recovery of regularity of cellular arrangement of scalp
corneocytes and the improvement of multi-layer desquamation Rating
of regularity of cellular arrange- Rating of multi-layer Sample
ment of corneocytes desquamation
______________________________________ Example 1 1.7 2.0 2 1.5 2.0
3 1.4 1.6 4 1.3 1.4 Comparative 4.1 4.5 Example 1
______________________________________
TABLE 13 ______________________________________ Results of tests
for the recovery of regularity of cellular arrangement of scalp
corneocytes Standard deviation Sample Rating score n = 10
______________________________________ Example 15 1.3 .+-.0.8
Comparative Example 6 3.2 .+-.0.9 ***
______________________________________ Test of significance:
Student's tTest Control: Example 15 *** P < 0.001
TABLE 14 ______________________________________ Results of tests
for the improvement of multi-layer desquamation Standard deviation
Sample Rating score n = 10 ______________________________________
Example 15 1.4 .+-.0.7 Comparative Example 6 3.1 .+-.0.6 ***
______________________________________ Test of significance:
Student's tTest Control: Example 15 *** P < 0.001
As is apparent from the test results shown in Tables 2, 13 and 14,
all the scalp essences formulated in accordance with Examples 1-4
and 15 gave ratings of 2.0 or less, thus being excellent in the
rate of recovery of the regularity of cellular arrangement of
corneocytes as well as in the improvement of multi-layer
desquamation.
Furthermore, in respect of the rate of recovery of the regularity
of cellular arrangement of corneocytes, good results are noted with
Examples 1, 2 and 15 where steroid glycoside, triterpenoid
glycoside, sphingo glycolipid and steroid hormone are incorporated,
as well as with Examples 3 and 4 where resorcin and resorcin and
pantethine are added to the ingredients mentioned above,
respectively. In contrast, the scalp essences formulated in
accordance with Comparative Example 6, where none of steroid
glycoside, triterpenoid glycoside and sphingo glycolipid is
incorporated, and Comparative Example 1, where none of steroid
glycoside, triterpenoid glycoside, sphingo glycolipid and estrone
is incorporated, gave ratings of more than 3.0, thus showing low
rates of recovery of the regularity of cellular arrangement of
corneocytes.
On the other hand, in respect of multi-layer desquamation, it is
noted that particularly excellent results are obtained with
Examples 3 and 4 where resorcin and resorcin and pantethine are
additionally incorporated, respectively, as well as with Example 15
where a larger amount of steroid hormone is used.
B. Visual observation of scalp lesions
Sample
Scalp essence from Example 1
Procedure
Ten healthy male subjects to be tested in their twenties to forties
have their hair cut with a hair-cutter and then get their head
shaved.
An aqueous solution of 0.5% sodium lauryl sulfate is applied to
cause lesions in the scalp. To some of these lesions is applied the
scalp essence from Example 1 twice a day from the following day for
consecutive seventeen days, while the other lesions are left
untreated without any application for spontaneous healing. After
seventeen days, specimens of desquamated stratum corneum are
prepared from the lesions, both treated and untreated, with an
adhesive tape. The state of healing is compared for evaluation by
observing the state of the stratum corneum under a microscope.
Where the scalp lesions are healed, the stratum corneum is peeled
uniformly and thinly, and where there still remain lesions, it is
peeled ununiformly and thickly.
Results
In the stratum corneum specimens obtained from the sites where the
scalp essence from Example 1 was applied, the phenomenon that the
stratum corneum is peeled ununiformly and thickly was found to
disappear apparently earlier than in those specimens obtained from
the sites where nothing was applied, the effect of recovering scalp
lesions thus being shown.
C. Test for hair moisturizing effect
Sample
Scalp essences from Examples 1-4 and Comparative Example 1.
Procedure
Fifty female subjects whose hair is damaged, glossless and dry due
to the use of permanent wave fluids are divided at random into five
groups of ten each.
After washing the hair with shampoos in ordinary use, a particular
sample, predetermined for each subject, is applied and such
application is repeated for three weeks.
Sensory evaluation was made by the subjects themselves.
Evaluation criteria
<Hair moisturizing effect>
.circleincircle.: Greatly improved
.smallcircle.: Improved
.DELTA.: Little changed
Results
TABLE 3 ______________________________________ Results of tests for
hair moisturizing effect Comparative Example Example Evaluation 1 2
3 4 1 ______________________________________ Moisturiz- persons
effect .circleincircle. 8 8 8 9 2 .smallcircle. 2 2 2 1 4 .DELTA. 0
0 0 0 4 ______________________________________
As is apparent from the test results indicated in Table 3 shown
above, 8-9 out of 10 subjects were evaluated to be
".circleincircle.(greatly improved)" in all the examples. Thus it
is shown that the product of the present invention has a
significant hair moisturizing effect as compared to that from the
Comparative Example.
Examples 5 and 6 and Comparative Example 2
Shampoo is prepared.
Formulation is shogun in Table 4.
TABLE 4 ______________________________________ Formulation of
Shampoo Comparative Example Example Raw materials 5 6 2
______________________________________ Coconut fatty acid
diethanolamide 2.5 2.5 2.5 ALSCOAP M-3S (Toho Chemical Industry
Co., Ltd.)*.sup.1 10.0 10.0 10.0 ANON GLM-R 8.0 8.0 8.0 (Nippon Oil
& Fats Co., Ltd.)*.sup.2 BISTAR CAP 8.0 8.0 8.0 (Matsumoto
Yushi-Seiyaku Co., Ltd.)*.sup.3 Polymer JR (Union Carbide)*4 0.5
0.5 0.5 Methyl para-hydroxybenzoate 0.2 0.2 0.2 Disodium edetate
0.1 0.1 0.1 Perfume 0.1 0.1 0.1 1,3-Butylene glycol 8.0 8.0 8.0
Product of Preparation 1 1.0 1.0 -- Estradiol 0.1 0.1 -- Lanolin --
-- 1.1 Purified water 61.5 61.2 61.5 Ginseng extract -- 0.1 --
Glycyrrhetinic acid -- 0.1 -- Allantoin -- 0.1 --
______________________________________ *.sup.1 30% aqueous solution
of sodium polyoxyethylene lauryl ether sulfate (3 E.O.) *.sup.2
2alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine *.sup.3
30% aqueous solution of coconut fatty acid amide
propyldimethylamino acetic acid betaine *.sup.4
Hydroxyethylcelluiose hydroxypropyltrimethyl ammonium chloride
ether
Method of Preparation
The raw materials in Table 4 are combined together and stirred well
at room temperature to give a homogeneous solution.
The shampoos formulated in accordance with Examples 5 and 6 and
Comparative Example 2 and the scalp essences formulated in
accordance with Examples 2 and 8 and Comparative Example 3 were
subjected to the following test for dandruff suppression
effect.
D. Test for dandruff suppression effect
Sample
Shampoos from Examples 5 and 6, and Comparative Example 2 and scalp
essences from Examples 2 and 8 and Comparative Example 3
Test Method
1) Fifteen subjects who were comparatively dandruffy were divided
at random into three groups of five each. The test was conducted
for a period of one month and the subjects washed the hair every
other day. In washing their hair, they used, for the first two
weeks, the shampoo from Comparative Example 2 as a control and
immediately thereafter the scalp essence from Comparative Example 1
and, for the subsequent two weeks, the shampoo from Example 5 or 6
or the one from Comparative Example 2 for the purpose of comparison
and immediately thereafter the scalp essence from Example 2 or, for
the purpose of comparison, the shampoo from Comparative Example 2
and immediately thereafter the scalp essence from scalp essence
from Comparative Example 1.
2) Twenty Subjects who were comparatively dandruffy were divided at
random into two groups of ten each. The test was conducted for a
period of one month and the subjects washed the hair every other
day. In washing their hair, they used, for the first weeks, the
shampoo from Comparative Example 2 and immediately thereafter the
scalp essence from Comparative Example 1 and, for the subsequent
two weeks, the shampoo from Example 5 and immediately thereafter
the scalp essence from Example 15 or, for the purpose of
comparison, the shampoo from Comparative Example 2 and immediately
thereafter the scalp essence from Comparative Example 6.
In test methods 1) and 2), collection of dandruff was carried out
as follows: The subjects were made to wash the hair over a meshwork
basket covered with a non-woven fabric. The non-woven fabric was
then air-dried to recover dandruff and hair as a residual solid on
the filter. After removal of the hair, the Collected dandruff was
dried under reduced pressure and its weight in mg was measured.
Method of Evaluation
Changes in dandruff weights were studied by comparing the mean dry
weight of dandruff obtained in the last two hair washings during
the use of the control with that obtained in the last two hair
washings during two weeks of use of the product of the present
invention or the control product.
The % reduction was determined using the following formula:
##EQU1##
Results
(i) Shampoo from Example 5
TABLE 5 ______________________________________ Results of Dandruff
Suppression Test (Example 5) Dandruff weight (mg) Subject Control
Example 5 Reduction (%) ______________________________________ 1
36.2 17.3 52.2 2 33.4 16.2 51.5 3 26.0 13.1 49.6 4 51.2 25.3 50.6 5
56.7 32.2 43.2 Mean 49.4 ______________________________________
As is apparent from Table 5, a significant dandruff suppression
effect was observed in all the five subjects, the mean percent
reduction being 49.4%.
(ii) Shampoo from Example 6
TABLE 6 ______________________________________ Results of Dandruff
Suppression Test (Example 6) Subject Control Example 5 Reduction
(%) ______________________________________ 1 34.6 13.8 60.1 2 31.4
13.5 57.0 3 23.0 11.0 52.2 4 52.1 25.3 51.4 5 58.5 26.1 55.4 Mean
55.2 ______________________________________
As is apparent from Table 6, a significant dandruff suppression
effect was observed in all the five subjects, the mean percent
reduction being 55.2%.
(iii) Comparative Example 2
TABLE 7 ______________________________________ Results of Dandruff
Suppression Test (Comparative Example 2) Dandruff weight (mg)
Comparative Reduction Subject Control Example 2 (%)
______________________________________ 1 35.5 22.0 38.0 2 31.2 21.4
31.4 3 25.0 16.2 35.1 4 47.0 33.4 28.9 5 59.1 40.0 32.3 Mean 33.1
______________________________________
As is apparent from Table 7, Comparative Example 2 gave the mean
percent dandruff reduction of 33.1% thus showing a poorer dandruff
reduction effect than in Examples 5 and 6.
(iv) Scalp essences from Example 15 and Comparative Example 6
TABLE 15 ______________________________________ Mean by weight of
dandruff (mg) Rating score Sample X .+-. S.D. n = 10
______________________________________ Example 15 20.5 .+-. 9.4
Comparative Example 6 34.2 .+-. 12.4 *
______________________________________ Test of significance:
Student's tTest Control: Example 15 *P < 0.05
As is apparent from Table 15, the scalp essence from Example 15 is
observed to give a significant dandruff suppression effect over the
one from Comparative Example 6.
Example 7
Tonic is prepared.
Formulation is shogun in Table 8.
TABLE 8 ______________________________________ Formulation of Tonic
Raw materials Example 7 ______________________________________ (1)
Ethanol 50 l-Menthol 0.2 Perfume 0.2 Polyoxyethylene hydrogenated
castor oil 0.5 (50 E.O.) Product of Preparation 1 0.5 Cortisone
0.02 dl-.alpha.-Tocopherol acetate 0.5 (2) Citric acid 0.13 Sodium
citrate 0.05 Purified water 46.9 Placentas extract 1.0
______________________________________
Method of Preparation
The raw materials indicated in (1) in Table 8 were mixed with and
dissolved in those indicated in (2) in Table 8 shown above with
stirring to prepare a tonic.
[External Skin Preparation]
Examples 8-14 and 16 and Comparative Examples 3-5 and 7-10 relate
to external skin preparation.
Example 8 and Comparative Examples 3-5 relate to oil-in-water type
cream.
Formulation is shown in Table 9.
TABLE 9
__________________________________________________________________________
Formulation of Oil-in-Water Cream Compara- Compara- Compara- tive
tive tive Example Example Example Example Raw materials 8 3 4 5
__________________________________________________________________________
(1) Squalane 13 13 13 13 Jojoba oil 3 3 3 3 Silicone oil 2 2 2 2
Behenic acid 2 2 2 2 Synthetic spermaceti 3 3 3 3 Polyoxyethelene
1.5 1.5 1.5 1.5 sorbitan monostearate (20 E.O.) Lipophilic glycerin
1.2 1.2 1.2 1.2 monostearate Product of 3 3 0 0 Preparation 1 (2)
1,3-Butylene glycol 5 5 5 5 Glycerin 3 3 3 3 Purified water 62.99
63 65.99 66 Methyl para- 0.1 0.1 0.1 0.1 hydroxybenzoate (3)
Estrone 0.01 0 0.01 0 Perfume 0.2 0.2 0.2 0.2
__________________________________________________________________________
Method of Preparation
The raw materials indicated in (1) in Table 9 and those indicated
in (2) in Table 9 shown above are separately dissolved by heating
them at 80.degree. C. A part of the solution from (2) is slowly
added with stirring to the solution from (1) and after reversal
emulsification the remainder of the solution from (2) is added. The
mixture is cooled down to 40.degree. C. and after addition of the
raw materials indicated in (3) further down to 30.degree. C.
Example 16 and Comparative Examples 7-10 relate to water-in-oil
type cream.
Formulation is shown in Table 16.
TABLE 16
__________________________________________________________________________
Formulation of Water-in-Oil Cream Compa- Compa- Compa- Compa-
rative rative rative Example rative Example Example Example Raw
materials 16 Example 7 8 9 10
__________________________________________________________________________
(1) Bees wax 5 5 5 5 5 Micro-crys- 6 6 6 6 6 talline wax Liquid 15
15 15 15 15 petrolatum Pyroglutamic 4 4 4 4 4 acid monooleate Butyl
para- 0.1 0.1 0.1 0.1 0.1 hydroxy benzoate Steroid 8 8 8 0 0
glycoside and triterpenoid glycoside Sphingo 2 2 0 2 0 glycolipid
(2) 4-O--.alpha.-D-gluco- 6 6 6 6 6 pyranal- sorbitol Purified
water 53.796 53.7 55.696 61.696 63.696 (3) Estrone 0.004 0 0.004
0.004 0.004 Dipotassium 0 0.1 0 0 0 glycyrrheti- nate Allantoin 0 0
0.1 0 0 Vitamin E 0 0 0 0.1 0 Sodium 0 0 0 0 0.1 hyaluronate
Perfume 0.1 0.1 0.1 0.1 0.1
__________________________________________________________________________
Results of the following tests A, B, B', C and C' will be shown
below which were carried out with the external skin preparation in
accordance with the present invention:
A: Test for the normalization and retardation of stratum corneum
turnover;
B: Test for the recovery of the regularity of cellular arrangement
of corneocytes;
B': Test for the improvement in multi-layer desquamation;
C: Visual observation for skin-roughening improvement effect;
and
C': Test for water content improvement effect by measurement of
skin surface conductance.
A. Test for the normalization and retardation of stratum corneum
turnover.
Sample
Oil-in-water type cream formulated in accordance with Example 8 and
Comparative Examples 3-5.
Procedure
The dansyl chloride method is employed. This method involves
binding dansyl chloride, which emits fluorescence when irradiated
with ultra violet, to corneocytes and determining the stratum
corneum turnover time from the rate of attenuation of the
fluorescence. Details of the dansyl chloride method are described
in G. L. Grove & A. M. Kligman, Stratum Corneum, p.191 (1983)
(Springer-Verlag Berlin Heidelberg New York).
Results
The results are as shown in FIGS. 1-4.
In FIG. 1, the external skin preparation from Comparative Example
3, where steroid glycoside, triterpenoid glycoside and sphingo
glycolipid are contained but steroid hormone is not contained, is
indicated by --.smallcircle.--, while the one from Comparative
Example 5, where none of steroid glycoside, triterpenoid glycoside,
sphingo glycolipid and steroid hormone is contained, is indicated
by --.dottedcircle.--. As is apparent from FIG. 1, the turnover,
which normally attenuates linearly, shows an exponential
attenuation in Comparative Example 5, whereas it is found in
Comparative Example 3 to show a linear attenuation and therefore to
be normalized. In the case of Comparative Example, however, little
function of retarding the stratum corneum turnover is observed.
As shown from FIG. 2, the external skin preparation from
Comparative Example 4, where steroid hormone is contained but none
of steroid glycoside, triterpenoid glycoside and sphingo glycolipid
is contained, is found to have the function of retarding the
turnover of irregularized stratum corneum, but to show an
exponential attenuation, i.e. little function of normalizing the
stratum corneum turnover.
As shown in FIG. 3, the external skin preparation from Example 8,
where steroid glycoside, triterpenoid glycoside, sphingo glycolipid
and steroid hormone are contained, is found to have the function of
normalizing and retarding the stratum corneum turnover.
As shown in FIG. 4, the external skin preparations from Comparative
Example 7, where none of steroid glycoside, triterpenoid glycoside
and steroid hormone is contained, and from Comparative Example 8,
where steroid glycoside and triterpenoid are contained but sphingo
glycolipid is not contained, are found to have the function of
normalizing, but little function of retarding, the stratum corneum
turnover. The external skin preparations from Comparative Example
9, where sphingo glycolipid and steroid hormone and contained but
none of steroid glycoside and triterpenoid glycoside is contained,
and from Comparative Example 10, where steroid hormone is contained
but none of steroid glycoside, triterpenoid glycoside and sphingo
glycolipid is contained, are found to have the function of
retarding the turnover of irregularized stratum corneum, but to
show an exponential attenuation, i.e. little function of
normalizing the stratum corneum turnover. In contrast, the external
skin preparation from Example 16, where steroid glycoside,
triterpenoid glycoside, sphingo glycolipid and steroid hormone are
contained, is found to have the function of normalizing and
retarding the stratum corneum turnover.
These effects of normalizing and retarding the stratum corneum
turnover bring about favorable effects on the skin, such as
improvement of skin-roughening or the like state. Furthermore,
these effects of improvement deserve special mention as outstanding
advantageous features which have never been achieved by the prior
art, since they do not merely improve the surface state of the skin
but they drastically better the skin as a whole from inside the
skin.
B. Test for the recovery of the regularity of cellular arrangement
of corneocytes.
Samples
Oil-in-water type cream formulated in accordance with Example 8 and
Comparative Examples 3-5.
Procedure
(1) A twenty four-hour closed patch test is carried out by sticking
on six different sites of the inside skin of the human upper arm
filter paper discs of 1.9 cm in diameter each containing 0.1 ml of
an aqueous solution of 0.5% (w/v) sodium lauryl sulfate.
There were used twenty healthy male subjects in their twenties to
forties.
By this treatment is produced a rough state of the skin, which
represents the irregulation of cellular arrangement of
corneocyte.
(2) After the treatment (1), the closed patches are removed.
Samples are applied twice a day, i.e. in the morning (at nine
o'clock) and in the evening (at seventeen o'clock), from the
following day for consecutive two months. In order to take into
account and avoid site to site variations, the site of application
is changed by rotation for each subject. The rate of daily recovery
is determined by observing specimens of the stratum corneum,
stripped off from the skin surface with an adhesive type, for the
regularity of cellular arrangement of corneocytes.
Samples
Water-in-oil type cream formulated in accordance with Example 16
and Comparative Examples 7-10.
Procedure
(1) A twenty four-hour closed patch test is carried out by sticking
on six different sites of the inside skin of the human upper arm
filter paper discs of 1.9 cm in diameter each containing 0. 1 ml of
an aqueous solution of 0.5% (w/v) sodium lauryl sulfate.
There were used ten healthy male subjects in their twenties to
forties.
By this treatment is produced a rough state of the skin, which
represents the irregulation of cellular arrangement of
corneocyte.
(2) After the treatment (1), the closed patches are removed.
Samples are applied twice a day, i.e. in the morning (at nine
o'clock) and in the evening (at seventeen o'clock), from the
following day for one consecutive month. In order to take into
account and avoid site to site variations, the site of application
is changed by rotation for each subject. The rate of daily recovery
is determined by observing specimens of the stratum corneum,
stripped off from the skin surface with an adhesive type, for the
regularity of cellular arrangement of corneocytes.
The regularity of cellular arrangement of corneocytes is judged by
the following five-grade rating:
Score
1. The cell shape is extremely uniform and the cellular arrangement
is extremely regular.
2. The cell shape is extremely uniform and the cellular arrangement
is regular.
3. The cell shape is slightly ununiform and the cellular
arrangement is intermediate.
4. The cell shape is ununiform and the cellular arrangement is
irregular.
5. The cell shape is entirely ununiform and the cellular
arrangement is extremely irregular.
Results
TABLE 10 ______________________________________ Standard deviation
Rating score n = 20 ______________________________________ Example
8 1.2 .+-.0.7 Comparative Example 3 2.3 .+-.1.1 Comparative Example
4 3.5 .+-.0.9 Comparative Example 5 3.9 .+-.1.0 Control with
nothing 4.4 .+-.1.0 applied
______________________________________
TABLE 17 ______________________________________ Standard deviation
Samples Rating score n = 10 ______________________________________
Example 16 1.5 .+-.0.5 Comparative Example 7 3.5 .+-.1.2***
Comparative Example 8 2.4 .+-.0.7** Comparative Example 9 3.0
.+-.0.6*** Comparative Example 10 3.2 .+-.0.6*** Control with
nothing 3.8 .+-.1.0*** applied
______________________________________ Test of significance:
Student's tTest Control: Example 16 **P < 0.01 ***P <
0.001
The results are shown in Tables 10 and 17 above. The rating scores
indicated in Tables 10 and 17 are those determined by statistical
processing of recovering effect ratings, obtained upon two months
of application of tested samples, on the basis of the five-grade
evaluation results in respect of the regularity of cellular
arrangement of corneocytes. The smaller the numerical rating score
is, the higher the rate of recovery is in terms of the regularity
of cellular arrangement of corneocytes.
From these test results, it is shown that Example 8 gives a higher
incidence of being rated as first than any of Comparative Examples
3-5 and also that its effect of recovery is significantly high
statistically. A significant difference was found between
Comparative Examples 3 and 4, but neither between Comparative
Examples 4 and 5 and a control with nothing applied nor between
Comparative Example 5 and the control. As is apparent from Table
17, the Example 16 gives a smaller rating score, showing a
statistically significant recovery of the regularity of cellular
arrangement of corneocytes as compared with Comparative Examples
7-10 and the control.
It was demonstrated from these results that the effect of
regularizing the cellular arrangement of corneocytes achieved when
steroid glycoside and/or triterpenoid glycoside and sphingo
glycolipid are contained but no steroid hormone is synergetically
increased by additionally incorporating steroid hormone.
B'. Test for the improvement in multi-layer desquamation
Samples
Water-in-oil type cream formulated in accordance with Example 16
and Comparative Examples 7-10.
Procedure
(1) A twenty four-hour closed patch test is carried out by sticking
on six different sites of the flexor aspect of the human forearm
filter paper disks of 1.9 cm in diameter each containing 0.1 ml of
an aqueous solution of 0.5% (w/v) sodium lauryl sulfate.
There were us ed ten healthy male subjects in their twenties to
forties.
By this treatment is produced a rough state of the skin, which
represents the irregulation of cellular arrangement of
corneocytes.
(2) After the treatment (1), the closed patches are removed.
Samples are applied twice a day, i.e. in the morning (at nine
o'clock) and in the evening (at seventeen o'clock), from the
following day for consecutive one month. In order to take into
account and avoid site to site variations, the site of application
is changed by rotation for each subject. The rate of daily recovery
is determined by observing specimens of the stratum corneum,
obtained from the skin surface with an adhesive tape, for
multi-layer desquamation.
Method of evaluation
The multi-layer desquamation is judged by the following five-grade
rating
Score
1. Small number (less than 5% of all) of cells are multi-layered
and densely stained.
2. Small number (5-10% of all) of cells are multi-layered and
densely stained.
3. Slightly large number (10-25% of all) of cells are multi-layered
and densely stained, and small number of cells are peeling in
masses.
4. Large number (25-50% of all) of cells are multi-layered and some
of them are peeling in masses.
5. Large number (50% or more of all) of cells are multi-layered and
masses of peeling cells are scattered all over.
The smaller the numerical score is, the less the multi-layer
desquamation of the stratum corneum is.
Results
TABLE 18 ______________________________________ Standard deviation
Samples Rating score n = 10 ______________________________________
Example 16 1.6 .+-.0.6 Comparative Example 7 3.2 .+-.0.9***
Comparative Example 8 2.6 .+-.0.3** Comparative Example 9 2.9
.+-.0.5*** Comparative Example 10 3.0 .+-.0.4*** Control with
nothing 3.6 .+-.0.9*** applied
______________________________________ Test of significance:
Student's tTest Control: Example 16 **P < 0.01 ***P <
0.001
As is shown in Table 18, the Example 16 is found to give a
statistically significant reduction, thus an excellent improvement,
in the multi-layer desquamation of corneocytes because of its
showing a smaller rating score than in Comparative Examples 7-10
and the control.
C. Visual observation for water content improvement effect.
Sample
Oil-in-water type cream from Example 8
Procedure
An aqueous solution of 0.5% sodium lauryl sulfate was applied to
the inside normal skin of the human upper arm to cause lesions
there. To some of such lesions is applied the external skin
preparation from Example 8 twice a day from the following day for
seventeen consecutive days, while the other lesions are left
untreated without any application for spontaneous healing. After
seventeen days, the skin-roughening improvement effect on lesions,
both treated and untreated, is evaluated by observing the state of
the stratum corneum under a microscope with specimens of
desquamated stratum corneum peeled off from the skin with an
adhesive tape. Where the skin is not roughened, the stratum corneum
is peeled uniformly and thinly, and where the skin is roughened, it
is peeled ununiformly and thickly.
In the stratum corneum specimens obtained from the sites where the
topical agent from Example 8 was applied, the phenomenon that the
stratum corneum is peeled ununiformly and thickly was found to
disappear apparently earlier than in those specimens obtained from
the sites where nothing was applied, the skin-roughening
improvement effect thus being shown.
C'. Test for water content improvement effect by measurement of
skin surface conductance
Sample
Water-in-oil type cream formulated in accordance with Example 16
and Comparative Examples 7-10.
Procedure
Method for the measurement of skin surface conductance:
Fifty female subjects who were subject to skin-roughening were
divided into five groups of ten subjects each. 5 .mu.g/cm.sup.2 of
sample predetermined for each group was applied, once a day, to the
flexor side of the human forearm for one month. After the subjects
were allowed to stand still for 40 minutes in a room kept at
20.degree. C. and a humidity of 50%, the skin surface conductance
was measured using a SKICON-200 (supplied by IBS).
The greater the value of conductance is, the higher the water
content is. The roughened skin is known to have a relatively low
water content as well as a relatively small value of
conductance.
Results
TABLE 19 ______________________________________ Measurement of skin
surface conductance (.mu..nu.) Rating score Samples X .+-. S.D. n =
10 ______________________________________ Example 16 19.2 .+-. 5.2
Comparative Example 7 15.0 .+-. 3.5 * Comparative Example 8 12.1
.+-. 4.7 ** Comparative Example 9 13.8 .+-. 4.0 * Comparative
Example 10 10.3 .+-. 3.5 *** Control with nothing 8.5 .+-. 5.6 ***
applied ______________________________________ Test of
significance: Student's tTest Control: Example 16 *P < 0.05 **P
< 0.01 ***P < 0.001
As is apparent from Table 19, the sample in accordance with the
present invention from Example 16 gives a statistically significant
increase in skin surface conductance comparing with the samples
from Comparative Examples 7-10 and the control, thus showing an
excellent improvement effect on the water content of the skin.
Examples 9-13
Water-in-Oil type cream is prepared.
Formulation is shown in Table 11.
TABLE 11
__________________________________________________________________________
Formulation of water-in-oil cream Exam- Example Example Exampl
Example Raw materials ple 9 10 11 e 12 13
__________________________________________________________________________
(1) Bees wax 5 5 5 5 5 Microcrystalline wax 6 6 6 6 6 Liquid
petrolatum 15 15 15 15 15 Pyroglutamic acid 4 4 4 4 4 monooleate
Butyl para-hydroxybenzoate 0.1 0.1 0.1 0.1 0.1 Steroid glycoside
and 8 8 8 8 8 triterpenoid glycoside Sphingo glycolipid 2 2 2 2 2
(2) 4-O--.alpha.-D-glucopyranal- 6 6 6 6 6 sorbitol Purified water
53.79 53.69 53.69 53.69 53.69 (3) Hydrocortisone acetate 0.01 0.01
0.01 0.01 0.01 Dipotassium 0 0.1 0 0 0 glycyrrhetinate Allantoin 0
0 0.1 0 0 Vitamin E 0 0 0 0.1 0 Sodium hyaluronate 0 0 0 0 0.1
Perfume 0.1 0.1 0.1 0.1 0.1
__________________________________________________________________________
Method of Preparation
The raw materials indicated in (1) in Table 11 are homogeneously
dissolved at 80.degree. C., and to the resultant solution are added
the ingredients indicated in (2) which had been homogeneously
dissolved at 80.degree. C. to form an emulsion. To the emulsion are
added, while cooling, the raw materials indicated in (3) at
40.degree. C., and the resultant mixture is cooled further down to
30.degree. C.
Example 14 Ointment
______________________________________ Formulation
______________________________________ Liquid paraffin 23.9
Vaseline 46.0 Polyoxyethylenesorbitan 4.0 monostearate (20 E.O.)
(1) Sorbitan monostearate 2.0 Steroid glycoside 0.8 Sphingo
glycolipid 0.2 Bees wax 3.0 Cetanol 1.0 Glycerin 10.0 (2) Purified
water 5.0 Estrone 0.01 (3) Allantoin 0.09 Purified water 4.0
______________________________________
Method of Preparation
The raw mate rials (1) and (2) in the formulation shown above are
separately heated at 80.degree. C. and then homogeneously mixed by
slowly adding (1) to (2) with stirring. The resultant mixture is
cooled down to 40.degree. C. and (3) is added.
Thus, by using the external skin preparations in accordance with
the present invention on the one hand, the turnover of the stratum
corneum of the skin can be normalized and retarded with the result
that the regularity of cellular arrangement of corneocytes can be
recovered and skin-roughening improved.
By using the scalp moisturizer in accordance with the present
invention on the other hand, the turnover of the stratum corneum of
the scalp can be normalized and this normalization effect leads to
the improvement of multi-layer desquamation as well as to the
recovery of cellular arrangement of corneocytes with the result
that dandruff production in the scalp can be suppressed and the
scalp moisturized.
* * * * *